The miR-58 microRNA family is regulated by insulin signaling and contributes to lifespan regulation in Caenorhabditis elegans.

microRNAs regulate diverse biological processes such as development and aging by promoting degradation or inhibiting translation of their target mRNAs. In this study, we have found that the miR-58 family microRNAs regulate lifespan in C. elegans. Intriguingly, members of the miR-58 family affect lifespan differently, sometimes in opposite directions, and have complex genetic interactions. The abundances of the miR-58 family miRNAs are up-regulated in the long-lived daf-2 mutant in a daf-16-dependent manner, indicating that these miRNAs are effectors of insulin signaling in C. elegans. We also found that miR-58 is regulated by insulin signaling and partially required for the lifespan extension mediated by reduced insulin signaling, germline ablation, dietary restriction, and mild mitochondrial dysfunction. We further identified the daf-21, ins-1, and isw-1 mRNAs as endogenous targets of miR-58. Our study shows that miRNAs function in multiple lifespan extension mechanisms, and that the seed sequence is not the dominant factor defining the role of a miRNA in lifespan regulation.